Haemostatic changes and thromboembolic risk during tamoxifen therapy in normal women

Abstract

SummaryTamoxifen has been implicated as a risk factor for venous thrombosis in advanced breast cancer although the evidence for increased arterial or venous thrombosis with tamoxifen in early breast cancer is less clear. The effect of tamoxifen on haemostasis, and thereby possible thromboembolic risk, was investigated in normal women enrolled in a placebo controlled trial of tamoxifen as a chemopreventative agent for breast cancer. There was an initial reduction in fibrinogen levels in all women on tamoxifen over the first year of follow-up and a marginal reduction in antithrombin III and Protein S in postmenopausal women at 6 months. There were no changes in cross linked fibrinogen degradation products or Protein C for pre or postmenopausal women. There was no increase in the incidence of thromboembolic events on tamoxifen. This study demonstrates that tamoxifen has only marginal effects on factors involved in haemostasis reported to affect the incidence of arterial or venous thromboembolic disease. The follow-up time is relatively short (maximum 36 months) and careful long term follow-up is necessary to detect clinically significant morbidity.

The Effects of Perioperative Tamoxifen Therapy on Microvascular Flap Complications in Transverse Rectus Abdominis Myocutaneous/Deep Inferior Epigastric Perforator Flap Breast Reconstruction

“…Tamoxifen induces a hypercoagulable state by decreasing certain anticoagulatory factors such as antithrombin III and proteins C and S. 11,12 Kelley et al 7 also hypothesized that the antagonism of tamoxifen at vascular ERs may lead to inhibition of vasodilation and inflammation secondary proliferation of endothelial smooth muscle. The contribution of tamoxifen in arterial thrombosis is less clear.…”

Tamoxifen, Raloxifene, and the Prevention of Breast Cancer*

“…At 70 months, no significant difference in the incidence of deep vein thrombosis or pulmonary embolism was observed between groups. A significant fall in total plasma cholesterol occurred within 3 months and was sustained over 5 yr of treatment (142, 213,214). The decrease affected low-density lipoproteins with no change in apolipoproteins A and B or high-density lipoprotein cholesterol.…”

Acute bilateral pulmonary emboli occurring while on adjuvant aromatase inhibitor therapy with anastrozole: case report and review of the literature

“…If it exerts purely agonist properties on the coagulation system, than an increased risk of VTE would be expected biologically, as an association between oral estrogens and VTE is well-documented [32,33]. However, it is not clear that tamoxifen's influence on the coagulation system is purely agonistic, as evidence for a possible antagonist effect comes from studies that showed no change in markers of activated coagulation or fibrinolysis, including prothrombin F 1.2 , fibrin degradation products (FDP), or thrombin-antithrombin complex (TAT) [26,27,31,34].…”

“…While the association between tamoxifen and increased risk of VTE is well-documented, the exact mechanism is Versus placebo unclear, with most studies, but not all, reporting significant decreases in levels of ATIII, protein C, and protein S [23][24][25][26][27][28][29][30][31]. As tamoxifen has mixed partial estrogen agonist/ antagonist properties, it is not known if tamoxifen exerts a purely estrogen agonist effect on the coagulation system.…”